Vnitr Lek 2014, 60(12):1095-1101

IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (studie IMPROVE-IT)

Jindřich Špinar^1,2,*, Lenka Špinarová³, Jiří Vítovec³

¹ Interní kardiologická klinika LF MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jindřich Špinar, CSc., FESC

² Mezinárodní centrum klinického výzkumu - Klinika kardiovaskulárních onemocnění FN u sv. Anny Brno, ředitel Gorazd B. Stonkin, M.D., MSc., Ph.D.

³ I. interní kardio-angiologická klinika LF MU a FN u sv. Anny Brno, přednostka prof. MUDr. Lenka Špinarová, CSc., FESC

Background:
The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is evaluating the potential benefit for reduction in major cardiovascular (CV) events from the addition of ezetimibe versus placebo to 40 mg/d of simvastatin therapy in patients who present with acute coronary syndromes and have low-density lipoprotein cholesterol (LDL-C) ≤ 125 mg/dl.

Methods:
Randomized double blind clinical trial in patients with acute coronary syndrome and low cholesterol level. The simvastatin monotherapy arm's LDL-C target was < 70 mg/dl, the comparison arm was simvastatin + ezetimibe. Ezetimibe was assumed to further lower LDL-C by 15 mg/dl and produce an estimated ~ 8 % to 9 % treatment effect. The primary composite end point was CV death, nonfatal myocardial infarction (MI), nonfatal stroke, rehospitalization for unstable angina (UA), and coronary revascularization (≥ 30 days postrandomization). The targeted number of events was 5,250.

Results:
18,144 patients were enroled with either ST segment elevation MI (STEMI, n = 5,192) or UA/non-ST segment elevation MI (UA/NSTEMI, n = 12,952) from October 2005 to July 2010. Primary endpoint occured in 2 742 patients (34.7 %) treated with simvastatin in monotherapy and in 2 572 patients (32.7 %) (p = 0.016) treated with combination. Compared to patients with coronary heart disease given the drug simvastatin plus a placebo, those given both simvastatin and the non-statin drug, ezetimibe, had a 6.4 % lower combined risk of subsequent heart attack, stroke, cardiovascular death, rehospitalization for unstable angina and procedures to restore blood flow to the heart. Heart attacks alone were reduced by 13 %, and non-fatal stroke by 20 %. Deaths from cardiovascular disease were statistically the same in both groups. Patients were followed an average of approximately six years, and some as long as 8.5 years. Approximately 2 patients out of every 100 patients treated for 7 years avoided a heart attack or stroke [Number Needed to Treat (NNT) = 50/7years].

Conclusions:
The study has shown a claer benefit from combination treatment with simvastatin and ezetimibe in patients with acute coronary syndrome and low LDL-C.

Keywords: acute coronary syndrome; combination therapy; ezetimibe; LDL-cholesterol

Received: December 1, 2014; Accepted: December 8, 2014; Published: December 1, 2014  Show citation